Rhodocytin, also called aggretin, is a platelet aggregation-inducing protein isolated from a venom gland of Calloselasma rhodostoma (non-patent document 1). Since the rhodocytin acts to aggregate platelets and then coagulate blood, it has been used for many studies to elucidate a platelet activation mechanism.
The platelets are small discoid blood cells and are indispensable for hemostasis and wound healing. When collagen or the like binds to platelet surface receptors, a signaling pathways are stimulated, resulting that platelet aggregation and blood coagulation are triggered by the stimulation. The rhodocytin has greatly contributed to the discovery of C-type lectin-like receptor 2 (CLEC-2) which is one of the platelet surface receptors (non-patent document 2). CLEC-2 has been reported to be associated not only with the platelet aggregation but also with cancer metastasis, lymphangiogenesis, inflammatory response and HIV seeding. In order to develop agents useful for the treatment of diseases associated with the platelet aggregation, there is a need for a method for enabling the identification of an agent effective for blocking the responses of the platelet surface receptors and their signaling pathways. Thus, it is necessary to identify the platelet surface receptors. Therefore, the studies of ligands (such as rhodocytin) that bind to the platelet surface receptors are essential for developing the agents useful for the treatment of the diseases associated with the platelet aggregation as described above.
The rhodocytin is snake venom isolated from Calloselasma rhodostoma. On the basis of the crystal structure analysis of the rhodocytin, it has been found that the rhodocytin is a secretory protein being a heterotetramer composed of rhodocytin a subunits and rhodocytin β subunits (non-patent document 3).
It has been reported that each of the rhodocytin α subunit and rhodocytin β subunit was encoded by a corresponding independent gene, which was cloned (non-patent document 4).